Abstract

Abstract Introduction Inability to discontinue chronic hypnotic use by people with insomnia remains a clinical concern. Sleep and hyperarousal was examined in an on-going “blinded” clinical trial in which people with insomnia are instructed to discontinue their study medication after 6 months of nightly use. Methods DSM-V diagnosed people with insomnia (n=31, 26 females), aged 23-61 yrs, with a polysomnographic sleep efficiency (SE) of ≤85% on a 8-hr polysomnogram, no other sleep disorders, unstable medical or psychiatric diseases or drug dependency have completed the clinical trial. Participants were randomized to zolpidem XR (12.5 mg), eszopiclone (3 mg) or placebo nightly for 6 months (blinded groups A: n=11, B: n=9, C: n=11). After 6 months, over a 2-week choice period, they were given the instruction to discontinue their nightly hypnotic use with an opportunity, if necessary, to self-administer either 1, 2, or 3 capsules of their assigned medication (zolpidem XR 6.25 mg as capsule 1, 6.25 mg as capsule 2, placebo as capsule 3; eszopiclone 2 mg, 1 mg, and placebo as capsules 1, 2 and 3 respectively; or 3 placebos. Results Fifteen subjects stopped taking study medication when told to discontinue. The other 16 subjects who took study medication (users) had longer MSLT (a measure of hyperarousal) sleep latency (16.2 vs 8.3 min) than non-users (p<.001) at baseline. At baseline users and non-users had similarly disturbed nocturnal sleep: SE 73.4 vs 73.9 %, with sleep latencies of 54 vs 40 min and wake time after sleep onset of 90 vs 104 min. Conclusion Hyperarousal, defined by MSLT and high diurnal urinary cortisol levels, has been found in some people with insomnia. High MSLTs were previously associated with dose escalation in a chronic zolpidem use study. These emerging data would suggest high MSLT may also be predictive of difficulty discontinuing hypnotic use. Support NIDA, grant#: R01DA038177 awarded to Dr. Roehrs

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